Systemic Metronidazole May Not Reduce Posthemorrhoidectomy Pain: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Hemorrhoidectomy is associated with significant postoperative pain. Oral metronidazole has been recommended as an adjunct to improve posthemorrhoidectomy analgesia. OBJECTIVE: This study aimed to evaluate the impact of oral metronidazole on patient-reported pain following hemorrhoidectomy. DATA SOURCES: We conducted a systematic search in the MEDLINE, EMBASE, ISI Web of Science, and Cochrane Central Register of Controlled Trials databases. STUDY SELECTION: Randomized controlled trials examining adults who underwent surgical hemorrhoidectomy were included. Participants in an active intervention group received oral metronidazole postoperatively, and those in a control group received placebo or usual care. Postoperative pain was assessed for at least 3 days postoperatively. INTERVENTION: A random-effects model was used. MAIN OUTCOMES MEASURES: The primary outcome was pain during the first 2 postoperative weeks, measured on a visual analogue scale. The secondary outcome was time to return to normal activities. RESULTS: Patients who received oral metronidazole had significantly lower reported pain scores on postoperative day 1 (standardized mean difference, -0.87 +/- 0.44; 95% CI, -1.73 to -0.015; p = 0.046; n = 4) and day 4 (standardized mean difference, -1.43 +/- 0.71; 95% CI, -2.83 to -0.037; p = 0.044; n = 3). Metronidazole use was associated with a significantly shorter time to return to normal activities (standardized mean difference, -0.76 +/- 0.34; 95% CI, -1.43 to -0.088, p = 0.027). The improvements disappeared in a sensitivity analysis excluding the largest trial with a high risk of bias, and no significance was observed during the remaining postoperative days. LIMITATIONS: The meta-analysis was limited by lack of double blinding, absence of a placebo, and unclear or high risk of bias in a proportion of the included trials. CONCLUSIONS: Although a favorable adverse effect profile supports consideration of oral metronidazole to reduce posthemorrhoidectomy pain, pooled analysis reveals inconsistent results with no pain reduction on most postoperative days. The current recommendation for routine prescription of oral metronidazole should be reevaluated in the absence of additional well-designed trials.